6-152975217-C-G

Variant names:

• chr6-152975217-C-G
• rs547843677
• NM_012177.5:c.508G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012177.5(FBXO5):​c.508G>C​(p.Gly170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G170S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXO5 NM_012177.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 1 publications found

Genes affected

FBXO5 (HGNC:13584): (F-box protein 5) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. This protein is similar to xenopus early mitotic inhibitor-1 (Emi1), which is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029079199).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012177.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO5	NM_012177.5	MANE Select	c.508G>C	p.Gly170Arg	missense	Exon 2 of 5	NP_036309.1	Q9UKT4-1
	FBXO5	NM_001142522.3		c.370G>C	p.Gly124Arg	missense	Exon 2 of 5	NP_001135994.1	Q9UKT4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO5	ENST00000229758.8	TSL:1 MANE Select	c.508G>C	p.Gly170Arg	missense	Exon 2 of 5	ENSP00000229758.3	Q9UKT4-1
	FBXO5	ENST00000367241.3	TSL:1	c.370G>C	p.Gly124Arg	missense	Exon 2 of 5	ENSP00000356210.3	Q9UKT4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.9
DANN	Benign	0.55
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.0	N
PhyloP100		0.36
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.037
Sift	Benign	0.57	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.14		Gain of helix (P = 0.0425)
MVP		0.17
MPC		0.37
ClinPred		0.028	T
GERP RS		0.19
Varity_R		0.067
gMVP		0.11
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs547843677; hg19: chr6-153296352;